C反应蛋白直接刺激人单核细胞肿瘤坏死因子α与白细胞介素6的表达
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Direct Proinflammatory Effect of C-Reactive Protein on Human Monocytes Isolated from Patients with Acute Coronary Syndrome
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    摘要:

    目的 比较急性冠状动脉综合征患者与健康人外周血单核细胞对一定浓度的C反应蛋白或细菌脂多糖刺激的炎症反应,并观察普伐他汀的干预效应。方法 采集并培养急性冠状动脉综合征患者(急性冠状动脉综合征组,n =15 )和健康志愿者(健康组,n =15 )的外周血单核细胞,分别用C反应蛋白(终浓度为2 0mg/L)或细菌脂多糖(终浓度10 μg/L)直接刺激2 4h。或用不同浓度(1、5和10 μmol/L)的普伐他汀预先孵育细胞2h ,再用C反应蛋白刺激。采用酶联免疫吸附试验法检测培养上清液中的肿瘤坏死因子α和白细胞介素6水平。结果 健康组受C反应蛋白刺激后肿瘤坏死因子α和白细胞介素6表达增加,分别为5 5 8±15 2ng/L和987±10 2ng/L ;受细菌脂多糖刺激后肿瘤坏死因子α和白细胞介素6增加显著,分别为10 5 4±371ng/L和185 4±4 6 7ng/L。急性冠状动脉综合征组受C反应蛋白刺激后肿瘤坏死因子α和白细胞介素6表达水平分别为15 5 4±784ng/L和312 9±333ng/L ;受细菌脂多糖刺激后分别为186 5±75 3ng/L和32 16±70 3ng/L。急性冠状动脉综合征组在1、5和10 μmol/L普伐他汀干预后,肿瘤坏死因子α表达分别下降14 %、36 %和4 9% ;白细胞介素6表达分别下降18%、2 6 %和36 % ,各亚组与C反应蛋白单独刺激组比较均有显著差异。健康组在普伐他汀干预后,肿瘤坏死因子α表达分别下降12 %、2 8%和4 5 % ;白细胞介素6表达分别下降15 %、2 2 %和31% ,各组间比较均有显著差异。结论 C反应蛋白与细菌脂多糖均能直接增加血单核细胞炎症因子的表达,有可能促进急性冠状动脉综合征及其并发症的发生。普伐他汀有效降低C反应蛋白对单核细胞的致炎症效应。

    Abstract:

    Aim The accumulating evidence suggests that C-reactive protein (CRP) may have direct inflammatory effects on the vascular wall and that statin therapy may have important non-lipid anti-inflammatory effects confirmed by decreasing serum inflammatory markers,such as CRP. However,the effect of pravastatin on tumor necrosis factorα (TNFα) and interleukin-6 (IL-6) release in cultured human monocytes from patients with acute coronary syndrome(ACS) was not investigated. Methods A prospective,human monocyte culture, pravastatin intervention study. Monocytes were isolated from blood of patients with acute coronary syndrome (ACS) and healthy volunteers by the Ficoll density gradient and stimulated by CRP (20 mg/L) or lipopolysaccharide (LPS,10 μg/L) for 24 h. Also 1 μmol/L,5 μmol/L,and 10 μmol/L pravastatin was coincubated with cells in the presence of CRP. Measurements of TNFα and IL-6 were performed from supernatants of cultured medium in duplicate,using a commercial assay kit. Results (1)CRP and LPS induced the release of TNFα and IL-6,with significantly elevated levels in cultured supernatants in ACS group and healthy group compared with their control group respectively.(2)A greater increase of TNFα and IL-6 induced by CRP and LPS were observed in the ACS group compared with the healthy group. Pravastatin inhibited significantly the production of TNFα and IL-6 in monocytes stimulated by CRP in a dose-dependent manner, a greater decrease was observed in ACS group compared with the control group(p<0.001). Conclusions CRP and LPS could induce more TNFα and IL-6 release in human monocyte from patients with ACS than from healthy volunteer. Pravastatin could inhibit this response in a dose-dependent manner in ACS group better than in healthy volunteer,which may provide an insight into the mechanisms of anti-inflammatory actions of pravastatin.

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王海蓉,黄从新,江洪,李建军,李庚山. C反应蛋白直接刺激人单核细胞肿瘤坏死因子α与白细胞介素6的表达[J].中国动脉硬化杂志,2005,13(2):199~202.

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  • 收稿日期:2004-05-11
  • 最后修改日期:2004-11-08
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